Thesis

The use of the wire hang test and a novel genotyping method to further determine the M712T mouse model

Hereditary Inclusion Body Myopathy (HIBM) is a disorder caused by a mutation in the GNE gene. Although there are 60 known mutations, this research study focused on the M712T mutation. The mutation causes complications in the production of sialic acid, and produces skeletal muscle wasting. The next step in the development of a cure is to produce an animal model. The purpose of this research study was to use the wire hang test to see if mice heterozygous and homozygous for the disorder developed strength deficits. I also tested a new method of genotyping that is faster and cheaper to perform than testing by restriction analysis. I used an animal model with the M712T mutation that was between 12-16 months of age. I tested their grip strength through the wire hang test. Also, I used an advanced rapid method of genotyping the mouse, which included designing two sets of primers specific for the mice GNE gene to determine which mutation the mice contained. The wire-hang test showed that the wild-type mice (WT) performed much better than both the heterozygote (HT) and mutants (MT). On average as a group, mutants performed the worst (32.62 s), followed by heterozygotes (47.35 s), and then wild-type mice (89.33 s). Moreover, the results show that there is a definite difference between the wild-type and mutant mice; both the mutant and heterozygous mice showed similar levels of strength, which indicates that even heterozygotes for the disorder suffer losses in skeletal muscle. Furthermore, my novel genotyping method also showed that it can reliably determine the genotype of the mice. This method is cheaper and quicker to perform.

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